Co-inheritance of α0-thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications

Introduction: Differentiation of homozygous hemoglobin (Hb) E with and without alpha(0)-thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A(2) is helpful. Methods: A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Results: Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/alpha(0)-thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A(2) were found, respectively, to be 4.97 +/- 0.69, 6.64 +/- 1.02, 4.86 +/- 0.87, and 7.60 +/- 1.04%. Among five couples at risk, alpha(0)-thalassemia was identified in three subjects with Hb A(2)>6.0%. Conclusions: Increased Hb A(2) level is a useful marker for differentiation of homozygous Hb E with and without alpha(0)-thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of alpha(0)-thalassemia in routine practice.